Standardized treatment of multiple myeloma 1. Initial treatment Smoldering myeloma and stage I multiple myeloma Smoldering myeloma is defined as M protein ≥30 g/L and/or plasma cells in bone marrow ≥10%, without symptoms of associated organ or tissue damage. Smoldering myeloma can be maintained for many years without treatment. Patients with stage I multiple myeloma have low M-protein levels and no significant anemia, hypercalcemia, or skeletal lesions. Smoldering myeloma and stage I multiple myeloma can last from a few months to a few years before disease progression, and these patients should be monitored clinically and followed up every 3-6 months. Multiple myeloma is treated according to the treatment plan of progressive stage multiple myeloma. Most patients with progressive multiple myeloma are found to have stage II or III myeloma, and initial treatment consists of conventional doses of chemotherapy and bisphosphonates. Eighty percent of these patients have bone disease, and 33% have kidney damage. For patients who are ready for transplantation, initial treatment options include vincristine + adriamycin + dexamethasone, thalidomide with or without dexamethasone, liposomal adriamycin + vincristine + dexamethasone, ralidomide + dexamethasone, bortezomib + dexamethasone, and bortezomib + adriamycin + dexamethasone. Initial treatment for patients not ready for transplantation includes dexamethasone monotherapy and thalidomide + dexamethasone regimens, mafran + prednisone, mafran + prednisone + thalidomide, and mafran + prednisone + bortezomib. The choice of thalidomide + dexamethasone as initial treatment was based on data from phase II trials (28 patients on thalidomide monotherapy and 40 patients on thalidomide + dexamethasone), with a remission rate of 72% and a complete remission rate of 16%. A randomized phase III clinical trial of 207 patients showed better remission rates in the thalidomide combined with dexamethasone group than in the dexamethasone group (58% vs. 41%). 60% remission rates were achieved with the MP regimen, with a maintenance period of 18 months and overall survival of 24-36 months. The remission rates for the initial combination chemotherapy and the MP regimen were the same, but the combination chemotherapy had a faster onset of action. Several recent phase II studies have shown that the addition of either thalidomide, bortezomib, or ralidomide to the MP regimen increases overall and complete remission rates, albeit at the cost of increased toxicities. In a phase III randomized clinical trial comparing the treatment effects of marfalan + prednisone + thalidomide with the MP regimen, the complete and/or partial remission rate was 7610% in the MP group and 16% in the MP group, and the 3-year survival rate was 80% in the MPT group and 64% in the MP group (P = 0119). This suggests that oral MPT can be an effective first-line treatment option for elderly patients with multiple myeloma. Stem cell toxicity factors such as nitrosoureas, alkylating agents and pelvic radiotherapy may affect stem cell collection and should therefore be avoided in patients who can undergo high-dose chemotherapy and stem cell transplantation. 3. For patients with primary refractory disease [defined as <50% reduction in serum M protein and/or new osteolytic lesions, or hypercalcemia, or <50% reduction in plasmacytoma volume], autologous stem cell transplantation should be considered as a priority, regardless of whether they are in clinical trials. Patients with primary refractory disease who are poorly treated initially have an overall efficiency of 92% and a progression-free survival rate of 70% at 1 year from the time of transplantation. Therefore, hematopoietic stem cell transplantation is recommended for patients with primary myeloma. Autologous hematopoietic stem cell transplantation Autologous hematopoietic stem cell transplantation is recommended for patients who have achieved remission or disease stabilization with initial therapy, and patients who have achieved remission or disease stabilization with salvage therapy. Cell sorting prior to autologous HSCT can reduce myeloma cell contamination but does not improve prognosis. If two stem cell transplants are planned, sufficient stem cells should be collected initially. Renal insufficiency and age are not contraindications to transplantation. Patients who have achieved remission after autologous HSCT may participate in clinical trials for post-transplant maintenance therapy. Failure or relapse after autologous stem cell transplantation may be treated with salvage therapy or allogeneic HSCT. Double autologous stem cell transplantation is also recommended. Thalidomide is 30% effective in patients who have relapsed after transplantation. Allogeneic HSCT can be used for young myeloma patients who have a human leukocyte antigen compatible donor. Allogeneic stem cell transplantation is available for patients who have achieved remission or stable disease with initial therapy, for patients who have achieved remission or stable disease with salvage therapy, for patients whose disease has progressed after autologous HSCT. Patients who are effective in high-dose chemotherapy and allogeneic HSCT can participate in clinical trials for maintenance therapy. Patients who do not achieve remission or relapse after allogeneic HSCT may receive donor lymphocyte infusion to obtain graft-versus-myeloma effect. Patients with disease progression after initial therapy should receive salvage therapy, and if relapse occurs after 6 months, the initial treatment regimen can be considered, and the salvage regimens are VAD, etoposide + dexamethasone + cytarabine + cisplatin, high-dose cyclophosphamide, thalidomide, thalidomide + dexamethasone, bortezomib, bortezomib + dexamethasone, ralidomide, ralidomide + dexamethasone, and dexamethasone. Patients who are effective in salvage therapy may still receive autologous or allogeneic hematopoietic stem cell transplantation. Treatment of complications Bone disease: 85% of patients with myeloma develop skeletal lesions that manifest as diffuse osteopenia and osteolytic lesions. A large double-blind randomized clinical trial has shown that monthly intravenous pamidronate reduces bone pain and skeletal-related complications, improves general condition, and most importantly, maintains quality of life in patients with stage III myeloma who have at least one osteolytic lesion. In 2007, the National Comprehensive Cancer Network recommended treatment with bisphosphonates for all patients presenting with skeletal lesions, including osteolysis. Patients on long-term bisphosphonates should be monitored for changes in renal function and for osteonecrosis of the jaw. Low-dose radiotherapy (10-30 Gy) can be used for uncontrolled. It can be used for palliative treatment of bone pain, possible pathologic fractures, or spinal cord compression. Consult an orthopedic specialist for patients who may have or have had a fracture of a weight-bearing bone, spinal compression of the spinal cord, or spinal instability. Spondyloplasty may be considered for symptomatic compression fractures of the spine. Other complications: hypercalcemia is treated with hydration, diuretics, diphosphonates, glucocorticoids, and calcitonin. Plasma exchange can be used as an adjunctive treatment for symptomatic hyperviscosity. Erythropoietin therapy can be given to patients with anemia, especially in the presence of renal failure, and endogenous erythropoietin levels can be measured to help determine the treatment plan. Infection is a relatively common complication in patients with multiple myeloma. For recurrent severe infections, intravenous immunoglobulin therapy is indicated. Prevention of Pneumocystis carinii pneumonia, herpes and fungal infections also needs to be considered if a high-dose dexamethasone regimen is used. Prophylaxis of herpes zoster needs to be considered when treating with bortezomib alone. Maintaining adequate hydration while avoiding nonsteroidal anti-inflammatory drugs may reduce the chance of renal insufficiency, but renal insufficiency is not a contraindication to transplantation. Thalidomide-based regimens or thalidomide and dexamethasone therapy need to be considered for prophylactic anticoagulation. Despite sensitivity to chemotherapy and radiotherapy, the disease is still incurable. Based on the published literature and several clinical trials, physicians can choose the optimal treatment that includes not only treatment of the underlying disease, but also supportive treatment to improve quality of life. With a better understanding of the biology of multiple myeloma, genetic and proteomic studies, there should be a further shift towards individualized treatment. The goal of treatment should be to achieve a relatively good clinical remission, preferably with CR, and to maintain this effect for as long as possible.